Interesting. I’ve never been on SSRIs but I have been interested in their mechanisms because for about eight years now I’ve had symptoms similar to PSSD, intense anhedonia to the point of not even having a fear response, etc. I consistently got brain zaps from 5 to 10mg Adderall XR back in the day (never took more than that in a day), and my neurological herpes prodrome features a few seconds of a very strong brain zap that feels like electric claws across the left side of my brain.
My Mitome showed iirc 11% function of Complex II + III, and low Complex IV. Based on the protocol I have been taking iron (HSV depletes it like crazy, and I have almost always had heavy periods) and L-cysteine (NAC just cements anhedonia for me) and the herpes prodrome vanished even though the iron triggered two or three outbreaks in a month. Also no sign of brain swelling, didn’t dysregulate my heart rhythm like usual.
I have permanent sexual dysfunction from Rexulti, and I've never heard about anyone else having the problems I do from Rexulti.
My take re: Adderall is the same take I have for Rexulti: they affect circuitry in the brain that is heavily involved in just about every process in the body in one way or another. So it's possible they could screw anything up.
I know one girl who's had PSSD for over 10 years, and she said that right before it fully kicked in, she had the highest libido she'd ever experienced in her life. Then it vanished. It reminds me of Charles Bonnet syndrome, which my grandma had. It's a syndrome where people losing their vision start having frightening hallucinations. It's a desperate attempt of the brain to self-stimulate its own visual centers, as they're shutting down from a lack of input. My grandma had glaucoma and as it progressed she started having these frightening hallucinations.
Sounds similar to my friend who had sky high, insane libido one night....and then it completely vanished, and has been gone for 10 years. Sounds like the medication she was on was shutting down the part of her brain associated with sexual arousal, and similar to the visual hallucinations, it was like a "last hurrah" -- a desperate attempt of the brain to self-stimulate a part of itself that's dying. Like yelling frantically and hurling a life raft to someone drowning in the ocean.
I had withdrawal from Rexulti where I had total anhedonia, and not just that, but inner akathisia and severe depersonalization. It was the worst and most unsettling event of my life, like an episode of Black Mirror. Lucky for me, it only lasted a bit over 2 months, as I remember.
It was like I woke up and was me again. Just one day out of the blue after 2 months. Sexual function never returned to normal but I distinctly remember feeling like "me" again. DAWS, maybe - Dopamine agonist withdrawal syndrome - but who knows.
I wonder if the brain zaps are similar to Charles Bonnet syndrome. I had "body buzzing" for lack of a better term, right before the sexual dysfunction from Rexulti kicked in, I think a week or so into taking it and after my psychiatrist titrated my dose higher. It was an awful, horrible feeling, like every cell in my body was vibrating, and I felt extremely depersonalized.
It was almost like a nightmare version of a body high from weed. Not everyone gets a marked "zap" or jarring physical indication that something is wrong, but some do. Makes me think of that syndrome and if it's some sort of failed attempt of the brain to revive itself or bring parts of itself back online that have been severely damaged and altered.
Total shot in the dark there but with how poorly any of this is understood it's as good a guess as any.
I also have been having terrible memory issues, terrible respiration problems, weight gain, adhd, apathy, anhedonia, and histamine issues after stopping 3 years of amitriptyline usage. I am looking for supplements to recover from it. Looking to find more about this really. Thank you for your work!
I have been fighting with low energy, respirational problems, terrible memory issues, adhd, apathy after stopping 3 years of amitriptyline usage. I am looking to hear to how can I change back or heal. Thank you for all! I want to subscribe and become a member soon definitely
Thanks for looking in to this, been suffering with Post finasteride syndrome and looking for help. I’ve been focusing on mitochondria and the microbiome and have seen a lot of improvements. Many people recover from PSSD with fecal matter transplants as well
This really hit home. I was on Effexor for 15 years and came off cold turkey. It was the most horrendous experience of my life, I didn't start feeling better till the 3rd year. I haven't fully recovered, I still have extreme fatigue when I exercise, muscle weakness, hypersensitivity, and what feels like a total mitochondrial crash. But I am so much better than I previously was. Nothing has ever explain it so well as your series has. I'm hoping to get the Mitome kit but I'm located in Canada. :(
Yeah it's horrible, doctors are so miss informed on this anyway. My doctor told me I'd be fine in 3 months coming off 15 years of antidepressants. Yeah okay buddy.
My Doctor told me these drugs were safer than Tic tacs. I’m off 11 years and doing horrible. I was a bit better last year. But this year is just horrible. I do think it’s the mito
Yes I would like info on how to heal as well. I got off zoloft and had terrible withdrawl so the med hopped me trying about 6 different ones that all made it worse until I finally said forget it and stopped all of them.
I suffer from Long covid, was put on antidepressants at the onset of my illness. Tapering mirtazapine has made me much worse over the passt year and I strongly believe it plays a role! I am waiting for a mito swab results, and have just received sequencing results. How can one get the mitochondrial insights from wgs? I didn’t find any reports for mitochondria on their webpage.
Great! I already arranged with mitome to send my mitoswab as soon as I get it from red labs. It gives me hope for the first time since getting sick 3.5 years ago
I too have Long Covid/MCAS/Dysauntonmia... I'm on 15 mg of Mirtazipine and extremely nervous about tapering off of it. I only know of doing drops very slowly. I already have mast cell issues so coming off this med will cause a storm. 🥴 I hope things get better and better for you!
Well, I regret taking it at all. It was given to me for insomnia, but stopped working. There is a facebook group mitrazapin withdrawal if you want to taper. Coming off from 7.5mg to 2.5mg over a year has made me worse, so not sure what to tell you.
Any thoughts on rapid detumescence (extremely rapid loss of erection upon ejaculation)? For almost six years I've had severe premature ejaculation and am unable to maintain an erection even for the duration of ejaculation, after being on Rexulti. I've done a recent interview with Moral Medicine on YouTube, as well as an older interview with the psychiatrist Josef Witt-Doerring, who has a channel on YouTube where he shares people's stories about PSSD.
Anyway, there is very little information online about penile detumescence after ejaculation, but check this out:
I've heard from other PSSD sufferers that rapid detumescence is common, though I've never heard anyone else use that clinical term. I think it's completely and utterly overlooked in terms of evaluating male sexual function.
For me, I somehow made it through Lexapro and Zyprexa, as well as many other medications, since 2002, seemingly without any permanent issues. However, in 2019, Rexulti got me. Rexulti is an atypical antipsychotic and its main mode of action is as a Dopamine D2 agonist, and 5-HT1A agonist, and as an antagonist at norepinephrine α1B, α2C, α1D, and α1A receptors.
Whether now or in the future, would love to know if you'd have any thoughts or insights. I don't have genital numbness, but I do have extremely severe premature ejaculation, combined with losing my erection *immediately* upon starting ejaculation. I can feel my erection going away as soon as ejaculation begins, and I am near fully flaccid within several seconds of starting an ejaculation.
The average is about 57 seconds after starting ejaculation, and I remember clearly that I used to stay erect for a couple minutes after ejaculating, and sometimes would not even lose my erection at all -- before the medication damage.
Post ejaculation penile detumescence is a completely overlooked feature of male sexual function, and my case might offer some very unique clues regarding PSSD, even though my dysfunction was from an antipsychotic medication.
Also worth mentioning I am compound heterozygous for MTHFR (C677T and A1298C). And also that I have permanent tinnitus, for well over a year now, after two small doses of Cialis taken over the course of two days. I think it was 10mg day 1, then 10mg again on day 2, whereupon I woke up around 2am with my ears ringing like crazy, and it has never stopped since.
I don't think I have bad luck, I think it's more likely that there are specific genetic sensitivities that might make people prone to these kinds of permanent damage. I'll also never know if my long history of Lexapro and Zyprexa somehow played a role in becoming permanently damaged from Rexulti later down the road.
Probably either depletion of serotonin and impaired GI motility or mitochondrial dysfunction impairing acidification and/or motility, transport, and sphincter function.
That is what it was like for the first few months, just pain, then it turned into severe ibs, like symptoms but cutting out fodmaps doesn't help, it's mostly high histamine foods that trigger me, but basically in the bathroom all the time...
Hi Chris, I have been following your SSRI series very closely, thank you for sharing your knowledge.
Would you have anything coming up about helping to get out of decades-long Cell Danger Response? I'm looking to do a mito.me but it seems that with a body stuck in CDR, every time I try to add nutrients (and my long list of supplements is very carefully curated), things get worse.
It feels like I've tried all the usual things and something key that I'm missing must do the trick.
There are limited tests to identify extracellular ATP, but there seem to be other markers in organic acid tests to suggest CDR. No, I don't have irrefutable proof, but years of trying to improve health and only finding that things aren't that much better after all that effort have made me look for answers beyond "this is lacking, so add it; then re-test and other things or the original is still lacking". It's frustrating to do the "right"/recommended things and to have paradoxical reactions. It's like a game of whack-a-mole. I'm looking forward to running a mito.me to see what the recommendations may be.
I'd love to get your take on the "stuck" CDR. Do you not think it's a "thing"? Please help me understand.
My 80yr old sister has been on Zoloft for years. After her husband died she realized she had no feelings (anhedonia) so her doctor changed her meds to another SSRI. It did not go well…. She spent time in a mental hospital. They changed her to Effexor and the severe mental issues calmed down. But.. she is now having a difficult time breathing, serious difficult time breathing. Specialist and tests with no answers. They found a small growth on her thalamus and had a Parathyroidectomy and thalamus removal. She was so frightened but went through with it so she could breathe. She could breath for a couple of day and now is as bad as ever.
So, your article came and I sent her a couple of paragraphs. Who would ever test for MADD and treat it? If she has 23_me raw data, could she find the gene?
In my early 20s stopped Zoloft cold turkey and drove van across country while withdrawing. Never touched it again lol. Depression isn’t fixed by SSRIs.
It’s an SSRI. Apparently invented as opposite effect of LSD. Can be used acutely for replenishing serotonin after drug use but otherwise stupid as lifestyle therapy.
Interesting. I’ve never been on SSRIs but I have been interested in their mechanisms because for about eight years now I’ve had symptoms similar to PSSD, intense anhedonia to the point of not even having a fear response, etc. I consistently got brain zaps from 5 to 10mg Adderall XR back in the day (never took more than that in a day), and my neurological herpes prodrome features a few seconds of a very strong brain zap that feels like electric claws across the left side of my brain.
My Mitome showed iirc 11% function of Complex II + III, and low Complex IV. Based on the protocol I have been taking iron (HSV depletes it like crazy, and I have almost always had heavy periods) and L-cysteine (NAC just cements anhedonia for me) and the herpes prodrome vanished even though the iron triggered two or three outbreaks in a month. Also no sign of brain swelling, didn’t dysregulate my heart rhythm like usual.
Still not sure why Adderall triggered brain zaps.
I have permanent sexual dysfunction from Rexulti, and I've never heard about anyone else having the problems I do from Rexulti.
My take re: Adderall is the same take I have for Rexulti: they affect circuitry in the brain that is heavily involved in just about every process in the body in one way or another. So it's possible they could screw anything up.
I know one girl who's had PSSD for over 10 years, and she said that right before it fully kicked in, she had the highest libido she'd ever experienced in her life. Then it vanished. It reminds me of Charles Bonnet syndrome, which my grandma had. It's a syndrome where people losing their vision start having frightening hallucinations. It's a desperate attempt of the brain to self-stimulate its own visual centers, as they're shutting down from a lack of input. My grandma had glaucoma and as it progressed she started having these frightening hallucinations.
Sounds similar to my friend who had sky high, insane libido one night....and then it completely vanished, and has been gone for 10 years. Sounds like the medication she was on was shutting down the part of her brain associated with sexual arousal, and similar to the visual hallucinations, it was like a "last hurrah" -- a desperate attempt of the brain to self-stimulate a part of itself that's dying. Like yelling frantically and hurling a life raft to someone drowning in the ocean.
I had withdrawal from Rexulti where I had total anhedonia, and not just that, but inner akathisia and severe depersonalization. It was the worst and most unsettling event of my life, like an episode of Black Mirror. Lucky for me, it only lasted a bit over 2 months, as I remember.
It was like I woke up and was me again. Just one day out of the blue after 2 months. Sexual function never returned to normal but I distinctly remember feeling like "me" again. DAWS, maybe - Dopamine agonist withdrawal syndrome - but who knows.
I wonder if the brain zaps are similar to Charles Bonnet syndrome. I had "body buzzing" for lack of a better term, right before the sexual dysfunction from Rexulti kicked in, I think a week or so into taking it and after my psychiatrist titrated my dose higher. It was an awful, horrible feeling, like every cell in my body was vibrating, and I felt extremely depersonalized.
It was almost like a nightmare version of a body high from weed. Not everyone gets a marked "zap" or jarring physical indication that something is wrong, but some do. Makes me think of that syndrome and if it's some sort of failed attempt of the brain to revive itself or bring parts of itself back online that have been severely damaged and altered.
Total shot in the dark there but with how poorly any of this is understood it's as good a guess as any.
Dear Chris Masterjohn, I literally just published a book on this yesterday: https://amazon.com/dp/B0FFBDCGP7
Please don't hesitate to reach out if you're interested in discussing the issue further.
I just watched your talk with Nicole Lambertson yesterday. Thank you for all your work to help us.
Do you believe that this mitochondrial dysfunction exists with benzodiazepine withdrawal also?
This is very valuable information. Thank you!
Dear Chris Masterjohn,
I literally just published a book on this yesterday: https://amazon.com/dp/B0FFBDCGP7
Please don't hesitate to reach out if you're interested in discussing the issue further.
Your book discusses how ssris effect the mitochondria?
I also have been having terrible memory issues, terrible respiration problems, weight gain, adhd, apathy, anhedonia, and histamine issues after stopping 3 years of amitriptyline usage. I am looking for supplements to recover from it. Looking to find more about this really. Thank you for your work!
I have been fighting with low energy, respirational problems, terrible memory issues, adhd, apathy after stopping 3 years of amitriptyline usage. I am looking to hear to how can I change back or heal. Thank you for all! I want to subscribe and become a member soon definitely
Thanks for looking in to this, been suffering with Post finasteride syndrome and looking for help. I’ve been focusing on mitochondria and the microbiome and have seen a lot of improvements. Many people recover from PSSD with fecal matter transplants as well
This really hit home. I was on Effexor for 15 years and came off cold turkey. It was the most horrendous experience of my life, I didn't start feeling better till the 3rd year. I haven't fully recovered, I still have extreme fatigue when I exercise, muscle weakness, hypersensitivity, and what feels like a total mitochondrial crash. But I am so much better than I previously was. Nothing has ever explain it so well as your series has. I'm hoping to get the Mitome kit but I'm located in Canada. :(
I just asked about the mito kit for Canada as I to live in Canada they don’t deliver due to customs
I'm considering taking a trip to the US if I have to.
It’s crazy how we can’t get the help here. Everything is damn hard.
Yeah it's horrible, doctors are so miss informed on this anyway. My doctor told me I'd be fine in 3 months coming off 15 years of antidepressants. Yeah okay buddy.
My Doctor told me these drugs were safer than Tic tacs. I’m off 11 years and doing horrible. I was a bit better last year. But this year is just horrible. I do think it’s the mito
When will you share the next article and will you provide steps on how one can improve from withdrawals
Yes I would like info on how to heal as well. I got off zoloft and had terrible withdrawl so the med hopped me trying about 6 different ones that all made it worse until I finally said forget it and stopped all of them.
I suffer from Long covid, was put on antidepressants at the onset of my illness. Tapering mirtazapine has made me much worse over the passt year and I strongly believe it plays a role! I am waiting for a mito swab results, and have just received sequencing results. How can one get the mitochondrial insights from wgs? I didn’t find any reports for mitochondria on their webpage.
I’ll release something for that later this year.
Great! I already arranged with mitome to send my mitoswab as soon as I get it from red labs. It gives me hope for the first time since getting sick 3.5 years ago
I too have Long Covid/MCAS/Dysauntonmia... I'm on 15 mg of Mirtazipine and extremely nervous about tapering off of it. I only know of doing drops very slowly. I already have mast cell issues so coming off this med will cause a storm. 🥴 I hope things get better and better for you!
Well, I regret taking it at all. It was given to me for insomnia, but stopped working. There is a facebook group mitrazapin withdrawal if you want to taper. Coming off from 7.5mg to 2.5mg over a year has made me worse, so not sure what to tell you.
Thank you for replying. It stopped working for me as well.
Any thoughts on rapid detumescence (extremely rapid loss of erection upon ejaculation)? For almost six years I've had severe premature ejaculation and am unable to maintain an erection even for the duration of ejaculation, after being on Rexulti. I've done a recent interview with Moral Medicine on YouTube, as well as an older interview with the psychiatrist Josef Witt-Doerring, who has a channel on YouTube where he shares people's stories about PSSD.
Anyway, there is very little information online about penile detumescence after ejaculation, but check this out:
https://pubmed.ncbi.nlm.nih.gov/40588622/
https://academic.oup.com/jsm/article-abstract/19/Supplement_4/S26/7464748?redirectedFrom=fulltext
I've heard from other PSSD sufferers that rapid detumescence is common, though I've never heard anyone else use that clinical term. I think it's completely and utterly overlooked in terms of evaluating male sexual function.
For me, I somehow made it through Lexapro and Zyprexa, as well as many other medications, since 2002, seemingly without any permanent issues. However, in 2019, Rexulti got me. Rexulti is an atypical antipsychotic and its main mode of action is as a Dopamine D2 agonist, and 5-HT1A agonist, and as an antagonist at norepinephrine α1B, α2C, α1D, and α1A receptors.
Whether now or in the future, would love to know if you'd have any thoughts or insights. I don't have genital numbness, but I do have extremely severe premature ejaculation, combined with losing my erection *immediately* upon starting ejaculation. I can feel my erection going away as soon as ejaculation begins, and I am near fully flaccid within several seconds of starting an ejaculation.
The average is about 57 seconds after starting ejaculation, and I remember clearly that I used to stay erect for a couple minutes after ejaculating, and sometimes would not even lose my erection at all -- before the medication damage.
Post ejaculation penile detumescence is a completely overlooked feature of male sexual function, and my case might offer some very unique clues regarding PSSD, even though my dysfunction was from an antipsychotic medication.
Also worth mentioning I am compound heterozygous for MTHFR (C677T and A1298C). And also that I have permanent tinnitus, for well over a year now, after two small doses of Cialis taken over the course of two days. I think it was 10mg day 1, then 10mg again on day 2, whereupon I woke up around 2am with my ears ringing like crazy, and it has never stopped since.
I don't think I have bad luck, I think it's more likely that there are specific genetic sensitivities that might make people prone to these kinds of permanent damage. I'll also never know if my long history of Lexapro and Zyprexa somehow played a role in becoming permanently damaged from Rexulti later down the road.
Do you have any idea why or how zoloft can cause gastritis that doesn't go away? Is there any way I can deal with this?
Probably either depletion of serotonin and impaired GI motility or mitochondrial dysfunction impairing acidification and/or motility, transport, and sphincter function.
I am dealing with this also after zoloft, it's been three years and I still can't eat most foods without issues.
Is your stomach always hurting? Mine stomach is completely numb with a weird pressure type pain in my stomach.
That is what it was like for the first few months, just pain, then it turned into severe ibs, like symptoms but cutting out fodmaps doesn't help, it's mostly high histamine foods that trigger me, but basically in the bathroom all the time...
Hi Chris, I have been following your SSRI series very closely, thank you for sharing your knowledge.
Would you have anything coming up about helping to get out of decades-long Cell Danger Response? I'm looking to do a mito.me but it seems that with a body stuck in CDR, every time I try to add nutrients (and my long list of supplements is very carefully curated), things get worse.
It feels like I've tried all the usual things and something key that I'm missing must do the trick.
What is your evidence this is due to “cell danger response” and what practical utility have you gotten from using that model?
There are limited tests to identify extracellular ATP, but there seem to be other markers in organic acid tests to suggest CDR. No, I don't have irrefutable proof, but years of trying to improve health and only finding that things aren't that much better after all that effort have made me look for answers beyond "this is lacking, so add it; then re-test and other things or the original is still lacking". It's frustrating to do the "right"/recommended things and to have paradoxical reactions. It's like a game of whack-a-mole. I'm looking forward to running a mito.me to see what the recommendations may be.
I'd love to get your take on the "stuck" CDR. Do you not think it's a "thing"? Please help me understand.
I don't think you have enough here to go down a rabbithole over it.
Thanks for your response.
Hey Chris,
Where can one get the Madd testing done?
My 80yr old sister has been on Zoloft for years. After her husband died she realized she had no feelings (anhedonia) so her doctor changed her meds to another SSRI. It did not go well…. She spent time in a mental hospital. They changed her to Effexor and the severe mental issues calmed down. But.. she is now having a difficult time breathing, serious difficult time breathing. Specialist and tests with no answers. They found a small growth on her thalamus and had a Parathyroidectomy and thalamus removal. She was so frightened but went through with it so she could breathe. She could breath for a couple of day and now is as bad as ever.
So, your article came and I sent her a couple of paragraphs. Who would ever test for MADD and treat it? If she has 23_me raw data, could she find the gene?
Thanks!
Judy
In my early 20s stopped Zoloft cold turkey and drove van across country while withdrawing. Never touched it again lol. Depression isn’t fixed by SSRIs.
Isn’t Fluoxetine a SNRI or it’s just a semantics?
It’s an SSRI. Apparently invented as opposite effect of LSD. Can be used acutely for replenishing serotonin after drug use but otherwise stupid as lifestyle therapy.